1. The Field of the Invention
The present invention relates to a mutant herpes simplex virus (HSV) ICP0 protein. More particularly, the present invention relates to a mutant HSV, mutant ICP0 protein, a vaccine or other composition having the mutant HSV and/or mutant ICP0, assay systems and reagents with the mutant HSV and/or mutant ICP0, and methods of making and using the same.
2. The Relevant Technology
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are two species of the herpes virus family, herpesviridae, which cause infections in humans. Members of herpesviridae infect humans to cause a variety of illnesses including cold sores, chickenpox or varicella, shingles or herpes zoster (VZV), cytomegalovirus (CMV), and various cancers, and can cause brain inflammation (encephalitis). All viruses in the herpes family produce life-long infections. HSV-1 and HSV-2 are also called Human Herpes Virus 1 and 2 (HHV-1 and HHV-2) and are neurotropic and neuroinvasive viruses; they enter and hide in the human nervous system, accounting for their durability in the human body. HSV-1 is commonly associated with herpes outbreaks of the face known as cold sores or fever blisters, whereas HSV-2 is more often associated with genital herpes.
An infection by a herpes simplex virus (HSV) is marked by watery blisters in the skin or mucous membranes of the mouth, lips, or genitals. Lesions heal with a scab characteristic of herpetic disease. However, the infection is persistent and symptoms may recur periodically as outbreaks of sores near the site of original infection. After the initial, or primary, infection, HSV becomes latent in the cell bodies of nerves in the area. Some infected people experience sporadic episodes of viral reactivation, followed by transportation of the virus via the nerve's axon to the skin, where virus replication and shedding occurs. Herpes is contagious if the carrier is producing and shedding the virus. This is especially likely during an outbreak but possible at other times. There is no cure yet, but there are treatments which reduce the likelihood of viral shedding.
HSV is a common and significant human pathogen which causes a variety of diseases, ranging from cold sores to potentially blinding ocular infections and life-threatening encephalitis. HSV establishes lifelong latent infections in neuronal cells, which reactivate periodically. The HSV lifecycle can be described in two specific stages of infection: latent and productive. Latent infection is defined as a lack of production of infectious virus at the site. Productive infection can be characterized by the expression of nearly all (about 100) viral genes in epithelial cells and fibroblasts at the periphery and the sensory neurons that innervate the site of infection. One of the important HSV-1 and HSV-2 proteins in this process is Infected Cell Protein 0 (ICP0).
Infected Cell Protein 0 (ICP0) is a nuclear phosphoprotein, and is one of the first HSV-1 proteins to be expressed upon infection of cells in culture. ICP0 is a key determinant in the switch between latent and productive infections of HSV viruses. ICP0 is a potent transactivator of HSV gene expression, and can be considered essential for efficient viral replication, especially at low multiplicities. ICP0 transactivates all classes of HSV genes, immediately-early (IE), early, and late, as well as numerous cellular genes and genes of other viruses. ICP0 is an immediately-early (IE) transactivator, and E3 ubiquitin ligase, which disrupts nuclear domain 10 and inhibits the cellular interferon response. Due to these features, HSV-1, HSV-2, and ICP0 have been studied for indications of the pathogenesis of the viral infection. Research of ICP0 has shown that phosphorylation is important for ICP0 to function in the viral pathway.